Herbicide resistance in weeds is an emerging threat to agriculture in Sub-Saharan Africa (SSA), though it remains underreported. High genetic diversity, wind pollination, and prolific seed production in regional weed species increase the risk of resistance evolution. Rising herbicide use, driven by labour shortages, monoculture systems, and limited access to diverse herbicide modes of action (MOAs), further contributes to resistance development. Despite low overall herbicide use, resistance cases are growing, particularly in South Africa, which has the region’s only formal monitoring body. Case studies on Amaranthus palmeri and A. hybridus highlight the development of resistance to multiple MOAs. However, a lack of trained weed scientists, inadequate surveillance, and limited reporting capacity across most SSA countries hinder early detection and response. To sustain agricultural productivity and food security, SSA must strengthen resistance monitoring, improve farmer training, and promote integrated weed management strategies combining chemical, mechanical, and cultural controls.